Introduction
Lumbar spondylolisthesis is a common spinal condition characterized by the anterior displacement of one vertebral body in relation to the one below it [1]. This condition has a variety of underlying causes, including degenerative changes, trauma, or developmental abnormalities such as an isthmic defect in the pars interarticularis [2]. Spondylolisthesis with an isthmic defect (isthmic spondylolisthesis) is often attributed to structural defects in the pars interarticularis, which are commonly congenital or caused by stress fractures [3]. In contrast, spondylolisthesis without an isthmic defect (commonly referred to as degenerative spondylolisthesis) typically results from intervertebral disc degeneration, facet joint osteoarthritis, or ligamentous laxity [4]. Differentiating between these two types is essential for identifying the underlying disease process and tailoring appropriate diagnostic and therapeutic strategies. Failure to recognize the presence of an isthmic defect may lead to misdiagnosis and suboptimal treatment.
Isthmic defects are most effectively visualized through computed tomographic (CT) imaging or oblique radiographs, which clearly depict the pars interarticularis [5,6]. However, magnetic resonance imaging (MRI) is the preferred modality for evaluating lumbar spine disorders, particularly those associated with disc degeneration [7], because it shows excellent soft tissue contrast and depicts associated changes in the lumbar spine. However, MRI has been reported to miss up to 30% of spondylolysis cases that are otherwise diagnosed on CT scans [8]. This diagnostic gap underscores the importance of identifying additional ancillary findings on MRI that could improve its diagnostic accuracy.
Results of previous studies have suggested that the finding of epidural fat (EF) interposition between the dura mater and the spinous process (posterior EF) on midsagittal MRI may be useful in the diagnosis of lumbar spondylolysis [9,10]. However, with regard to ancillary MRI observations, particularly those that could reliably distinguish between isthmic and degenerative spondylolisthesis, the literature is sparse. Clinically, our team has observed that many patients with lumbar spondylolysis display increased EF accumulation between the posterior margin of the vertebral body and the dura mater (anterior EF) on midsagittal MRI. This distinct localization inspired our assessment of the significance of anterior EF in identifying lumbar spondylolysis. We also investigated differences in anterior EF incidence and characteristics between patients with isthmic and nonisthmic spondylolisthesis, with a focus on analyzing anterior EF shapes to enhance diagnostic accuracy.
Therefore, our primary objective was to determine whether the finding of anterior EF on midsagittal MRI could reliably enable clinicians to differentiate isthmic from degenerative lumbar spondylolisthesis. We hypothesized that anterior EF, particularly with acute triangular structure, would be significantly more prevalent among patients with isthmic spondylolisthesis than among those with degenerative disease and would thereby be of diagnostic value.
Materials and Methods
All methods used in this retrospective study were in accordance with the Declaration of Helsinki, and this study was approved by the ethics committee of the Second Affiliated Hospital, Zhejiang University School of Medicine (approval no., 20240472). The participants provided written informed consent for their data to be analyzed and published.
Patient population
We retrospectively reviewed radiographic and clinical data of patients with lumbar spondylolisthesis that were collected at our institution from January to April 2024. CT scanning is part of our institution’s routine imaging protocol for evaluating lumbar spondylolisthesis. Criteria for inclusion in this study were (1) age of ≥18 years; (2) diagnosis of L3–L5 spondylolisthesis with available lumbar CT and MRI performed within 1 month of each other; and (3) involvement of a single motion segment. We excluded data from patients with a history of lumbar surgery, those with a spinal infection or tumor, those with multiple-level spondylolisthesis, and those whose MRI or CT images were of poor quality.
Imaging evaluation
Posterior EF was defined as the presence of fat tissue interposed between the spinous process and the dura mater [9,10] (Fig. 1), whereas anterior EF was defined as fat interposed between the posterior margin of the affected vertebral body and the dura mater. Anterior EF structure was further classified according to three distinct shapes: acute triangle (Fig. 2), obtuse triangle (Fig. 3), and oval (Fig. 4).
The presence of lumbar isthmic defects was determined by two senior spine surgeons according to bilateral pars interarticularis fractures visible on CT scans. Patients were then classified into two groups: those with isthmic spondylolisthesis and those with degenerative spondylolisthesis. Before CT evaluation, two experienced spine surgeons independently reviewed midsagittal T1- and T2-weighted MRI scans to assess the presence of anterior and posterior EF, as well as the structure of anterior EF. To minimize bias, the diagnosis based on CT scans was reviewed only after the MRI assessment was completed. Discrepancies in EF identification or classification were resolved by consensus. Each reviewer had >10 years of experience in spinal imaging interpretation.
Statistical analysis
Data for continuous variables were calculated as means±standard deviations, and those for categorical variables, as percentages. To assess the normality of continuous data, we used the Shapiro-Wilk test. For group comparisons, we used the chi-square test to analyze categorical variables; depending on the distribution, we compared continuous variables by using either the independent-samples t-test (for normally distributed data) or the Mann-Whitney U test (for nonnormally distributed data). To identify predictors of isthmic spondylolisthesis, we used multivariable logistic regression analysis and calculated odds ratios and 95% confidence intervals. To evaluate the diagnostic utility of anterior EF, we assessed sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy, and we used the receiver operating characteristic (ROC) curve to assess the discriminatory ability of anterior EF, quantified by the area under the curve. For all statistical and descriptive analysis, we used IBM SPSS Statistics for Windows ver. 27.0 (IBM Corp., Armonk, NY, USA). A p-value of <0.05 was considered statistically significant.
To evaluate interobserver agreement for EF presence and shape classification, we used Cohen’s kappa coefficient and interpreted the results according to Landis and Koch’s criteria, whereby values of >0.60 indicate substantial agreement and those of >0.80, almost perfect agreement. The kappa values were 0.76 for anterior EF and 0.73 for posterior EF; both thus reflected substantial agreement. For anterior EF structure, the kappa value was 0.68, which indicated moderate to substantial consistency. Discrepancies were noted in 15 cases (5.5%), including four for anterior EF presence, five for posterior EF presence, and six for anterior EF structure, all of which were resolved through consensus.
Results
Patient characteristics
A total of 274 patients with lumbar spondylolisthesis were included in this retrospective study; 129 (62 men, 67 women; mean age, 58.41±12.90 years) had isthmic spondylolisthesis, and 145 (76 men, 69 women; mean age, 65.96±9.27 years) had degenerative spondylolisthesis. As a group, patients with isthmic spondylolisthesis were significantly younger than those with degenerative spondylolisthesis (p<0.001). Gender distribution did not differ significantly between groups (p=0.472). Body mass indices of the two groups were comparable (24.58±2.57 kg/m2 for patients with isthmic disease and 25.02±2.37 kg/m2 for those with degenerative disease; p=0.133). Meyerding grade II spondylolisthesis was more prevalent in the isthmic group (15.5%) than in the degenerative group (5.5%; p=0.006) (Table 1).
Affected levels
The distribution of affected vertebral levels differed significantly between groups (p<0.001). Among the 129 patients with isthmic spondylolisthesis, the L5 level was most commonly affected (n=99; 76.7%), followed by L4 (n=29; 22.5%) and L3 (n=1; 0.8%). In contrast, among the 145 patients with degenerative spondylolisthesis, the L4 level was predominantly affected (n=121; 83.4%), followed by L3 (n=13; 9.0%) and L5 (n=7; 7.6%) (Table 1).
Presence of EF
Anterior EF was observed in 123 (95.3%) of the patients with isthmic spondylolisthesis cases but in only 41 (28.3%) of those with degenerative spondylolisthesis; this difference was highly significant (p<0.001). Anterior EF had 95.3% sensitivity, 71.7% specificity, a positive predictive value of 75.0%, a negative predictive value of 94.5%, and 82.8% overall diagnostic accuracy for identifying isthmic spondylolisthesis. Posterior EF was present in 105 (81.4%) of the patients with isthmic spondylolisthesis and 124 (85.5%) of those with degenerative spondylolisthesis; the difference was not significant (p=0.358) (Table 1). The area under the ROC curve for anterior EF as a predictor of isthmic spondylolisthesis was large, which indicated that anterior EF had excellent discriminatory ability (Fig. 5). Thus, anterior EF is a robust diagnostic marker, capable of reliably distinguishing isthmic from degenerative spondylolisthesis in clinical practice, and its use as a diagnostic marker can potentially reduce the rate of misdiagnosis and thereby aid in precise treatment planning.
Multivariable logistic regression analysis
Multivariable logistic regression analysis revealed that anterior EF was a strong predictor of isthmic spondylolisthesis (odds ratio, 38.730; 95% confidence interval, 11.655–128.702; p<0.001). Other significant predictors included younger age (p<0.001) and higher Meyerding grade (p=0.040). Gender (p=0.342), body mass index (p=0.333), level of spondylolysis (p=0.745 for L4 vs. L3; p=0.059 for L5 vs. L3), and posterior EF (p=0.776) were not significant predictors (Table 2).
Anterior EF shape analysis
The structure of anterior EF differed significantly between groups (p<0.001). Among patients with isthmic spondylolisthesis, the predominant shape was acute triangular (n=97; 75.2%), followed by obtuse triangular (n=22; 17.1%) and oval (n=4; 3.1%); anterior EF was absent in six patients (4.7%). Among patients with degenerative spondylolisthesis, the shape of EF was acute triangular in 25 (17.2%) and obtuse triangular in 16 (11.0%); no oval EF was detected, and anterior EF was absent in 104 patients (71.7%) (Table 3).
Discussion
In this study, we found that anterior EF, located between the posterior vertebral body margin and the dura mater on sagittal MRI, was a valuable imaging marker for differentiating isthmic and degenerative lumbar spondylolisthesis. The marked prevalence of anterior EF among isthmic cases (95.3%) versus degenerative cases (28.3%), coupled with its predominantly acute triangular structure in the former, underscores its diagnostic value. Multivariable logistic regression analysis confirmed that anterior EF was an independent predictor of isthmic spondylolisthesis; this finding highlights its critical role in enhancing diagnostic precision. With excellent sensitivity, specificity, and a large area under the ROC curve, anterior EF is a reliable tool for optimizing clinical diagnosis and treatment planning.
Early and accurate identification of isthmic spondylolisthesis is crucial for guiding appropriate treatment strategies and providing patients with informed prognostic expectations [11–13]. Whereas isthmic spondylolisthesis may remain stable with appropriate management, degenerative spondylolisthesis often progresses as a result of ongoing structural deterioration [4,14]. MRI has become the preferred modality of first-line imaging for spinal disorders because soft tissue contrast is excellent and multiple anatomical structures can be evaluated simultaneously. Differentiating between isthmic and degenerative spondylolisthesis on the basis of MRI features can facilitate timely and targeted clinical interventions, which can potentially improve long-term outcomes. However, MRI may fail to detect pars interarticularis defects, especially in early or subtle cases. In this context, anterior EF as an adjunctive sign supports the diagnosis of isthmic spondylolisthesis. Our findings align with those of prior studies in which ancillary MRI signs showed diagnostic value in identifying isthmic spondylolisthesis [15–18]. For example, Karan and Güdü [19] reported that combining direct visualization of pars defects with ancillary findings, particularly posterior EF, can enhance diagnostic sensitivity. However, their study did not address anterior EF. Building on this foundation, we showed that anterior EF is a novel MRI marker for differentiating isthmic from degenerative spondylolisthesis, characterized by high sensitivity and moderate specificity and an excellent complement to established ancillary signs.
Unlike prior studies in which posterior EF was emphasized as a potential sign of spondylolysis [9,20,21], our findings suggest that posterior EF lacks specificity in distinguishing between isthmic and degenerative subtypes. This discrepancy may be attributed to differences in study design. In previous research, patients with spondylolysis were often compared with individuals who had no symptoms or with patients who had degenerative disc disease, whereas our study included only patients with confirmed spondylolisthesis. By focusing on this cohort, we were able to more precisely evaluate the diagnostic relevance of anterior EF within the context of lumbar slippage. The formation mechanisms of anterior and posterior EF are similar, both potentially resulting from localized expansion of the epidural space. However, anterior EF is more likely to be associated with vertebral slippage, which increases the gap between the posterior vertebral body margin and the dural sac. This anatomical alteration facilitates distinct fat accumulation, which often manifests in the shape of an acute triangle. Such a characteristic structure is more frequently observed in isthmic spondylolisthesis and may provide greater diagnostic specificity. Other MRI features that distinguish isthmic from degenerative spondylolisthesis include the “step-off” sign, the “wide canal” sign, T2 cortical bone signal, and fluid in facet joints [22]. In the future, investigators should assess the diagnostic value of combining anterior EF with other ancillary signs to establish a more comprehensive MRI-based diagnostic protocol for isthmic lumbar spondylolisthesis.
The shape of anterior EF might enhance its diagnostic value. In our study, an acute triangle was the shape of anterior EF most frequently observed in patients with isthmic spondylolisthesis. This structure may reflect localized anterior dural displacement as a result of vertebral slippage and may serve as a supportive imaging feature on MRIs for isthmic disease. One possible explanation for the predominance of the acute triangular structure is that the majority of patients in our cohort had Meyerding grade I spondylolisthesis, which indicated relatively mild slippage. This limited degree of displacement may result in a sharply defined anterior epidural space that favors the formation of acute triangular fat deposition.
Despite its strengths, this study has several limitations. First, it was retrospective and conducted in a single center, which may limit the generalizability of the findings. Second, although anterior EF was assessed by experienced spine surgeons, broader validation through multicenter studies with larger and more diverse cohorts is necessary. Third, although anterior EF had excellent sensitivity (95.3%) for identifying isthmic spondylolisthesis, its specificity was moderate (71.7%). Future studies incorporating additional imaging features or patient demographic variables may help improve diagnostic accuracy. Moreover, although we identified three distinct anterior EF shapes, their clinical significance remains uncertain and should be assessed in future studies. Finally, researchers should explore the application of automated image analysis tools to enhance the detection and quantification of anterior EF in routine clinical practice.
Conclusions
This study demonstrates that anterior EF visible on MRI is a reliable marker for distinguishing isthmic from degenerative lumbar spondylolisthesis because of its high prevalence and characteristic acute triangular structure in isthmic cases. Because MRI may miss pars defects, anterior EF is a useful additional sign that can enhance diagnostic accuracy, reduce the need for CT or oblique radiographs, and assist in surgical planning. Integrating anterior EF assessment into routine MRI reading may lead to earlier diagnosis and improve patient outcomes.
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